Drug-induced chylothorax as a rare pleural complication in dasatinib therapy for chronic myeloid leukaemia.

Chylothorax is a lymphatic chylous pleural effusion typically associated with traumatic (iatrogenic, non-iatrogenic) and non-traumatic (infections, malignancy, lymphatic disorders) aetiologies. Drug-induced chylothorax is uncommon and mostly reported in association with BCR-ABL tyrosine kinase inhibitor therapy.

Transitioning to Combined EBUS EUS-B FNA for Experienced EBUS Bronchoscopist.

Endobronchial ultrasound (EBUS) combined with trans-esophageal endoscopic ultrasound bronchoscope guided fine need aspirate (EUS-B FNA) of mediastinal lymph nodes is an established procedure for diagnosis. The main barrier to a combined EBUS EUS-B FNA approach is availability of trained and accredited pulmonologist who can perform procedure safely and confidently. To address this gap, we undertook a training program for experienced EBUS bronchoscopists to train, learn, and incorporate combined EBUS EUS-B FNA into their procedural practice. Thirty-two patients were selected based on CT and or PET findings. Four experienced bronchoscopists participated by reading through learning material, observing 5 cases before performing EUS-B FNA under direct supervision. Forty-one lymph nodes and 6 non-nodal lesions were sampled. EUSAT assessment was performed by supervisor. Learning curves were derived from assessment scores. We observed that learning curve tends to plateau when participant can perform 3 or more consecutive cases with EUSAT score above 50. There were no complications. Our experience suggests that there is relative ease in transition to combined EBUS EUS-B TBNA procedures for mediastinal lymphadenopathy and lung cancer diagnosis and staging for experienced bronchoscopist using a program which incorporates direct supervision, EUSAT assessment, and extension of EUS B FNA training into daily real-world practice.

Impact of structured curriculum with simulation on bronchoscopy.

BACKGROUND AND OBJECTIVE: Simulation enhances a physician's competency in procedural skills by accelerating ascent of the learning curve. Training programmes are moving away from the Halstedian model of 'see one, do one, teach one', also referred as medical apprenticeship. We aimed to determine if a 3-month structured bronchoscopy curriculum that incorporated simulator training could improve bronchoscopy competency among pulmonary medicine trainees. METHODS: We prospectively recruited trainees from hospitals with accredited pulmonary medicine programmes. Trainees from hospitals (A, B and C) were assigned to control group (CG) where they received training by traditional apprenticeship while trainees from hospital D were assigned to intervention group (IG) where they underwent 3-month structured curriculum that incorporated training with the bronchoscopy simulator. Two patient bronchoscopy procedures per trainee were recorded on video and scored independently by two expert bronchoscopists using the modified Bronchoscopy Skills and Tasks Assessment Tool (BSTAT) forms. A 25 multiple choice questions (MCQ) test was administered to all participants at the end of 3 months. RESULTS: Eighteen trainees participated; 10 in CG and eight in IG with equal female:male ratio. Competency assessed by modified BSTAT and MCQ tests was variable and not driven by volume as IG performed fewer patient bronchoscopies but demonstrated better BSTAT, airway anaesthesia and MCQ scores. Bronchoscopy simulator training was the only factor that correlated with better BSTAT (r = 0.80), MCQ (r = 0.85) and airway anaesthesia scores (r = 0.83), and accelerated the learning curve of IG trainees. CONCLUSION: An intensive 3-month structured bronchoscopy curriculum that incorporated simulator training led to improved cognitive and technical skill performance as compared with apprenticeship training.

A man with pleural effusion and ascites.

A male lifelong nonsmoker aged 58 years with no prior asbestos exposure complained of gradual worsening breathlessness over 3 months. This was associated with abdominal and leg swelling and a 2-kg weight loss. He had no fever, night sweats, hemoptysis, joint pain, rash, abdominal pain, chest pain, or orthopnea. The patient had no recent travel or contact with pulmonary TB. He had stage I left-side testicular seminoma treated with left-sided radical orchidectomy 10 years previous and recently received a diagnosis of Child's B alcoholic liver cirrhosis. His hepatitis B and C screen result was normal.

Bedside pleural procedures by pulmonologists and non-pulmonologists: a 3-year safety audit.

BACKGROUND AND OBJECTIVE: Pleural procedures such as tube thoracostomy and chest aspirations are commonly performed and carry potential risks of visceral organ injury, pneumothorax and bleeding. In this context limited information exists on the complication rates when non-pulmonologists perform ultrasound-guided bedside pleural procedures. Bedside pleural procedures in our university hospital were audited to compare complication rates between pulmonologists and non-pulmonologists. METHODS: A combined safety approach using standardized training, pleural safety checklists and ultrasound-guidance was initially implemented in a ∼1000-bed academic medical centre. A prospective audit, over approximately 3.5 years, of all bedside pleural procedures excluding procedures done in operating theatres and radiological suites was then performed. RESULTS: Overall, 529 procedures (295 by pulmonologists; 234 by non-pulmonologists) for 443 patients were assessed. There were 16 (3.0%) procedure-related complications, all in separate patients. These included five iatrogenic pneumothoraces, four dry taps, four malpositioned chest tubes, two significant chest wall bleeds and one iatrogenic hemothorax. There were no differences in complication rates between pulmonologists and non-pulmonologists. Presence of chronic obstructive pulmonary disease (COPD) independently increased the risk of complications by nearly sevenfold. CONCLUSIONS: Results from this study support pleural procedural practice by both pulmonologists and non-pulmonologists in an academic medical centre setting. This is possible with a standard training program, pleural safety checklists and relatively high utilization rates of ultrasound guidance for pleural effusions. Nonetheless, additional vigilance is needed when patients with COPD undergo pleural procedures.

Effect of a pleural checklist on patient safety in the ultrasound era.

BACKGROUND AND OBJECTIVE: Bedside ultrasound allows direct visualization of pleural collections for thoracentesis and tube thoracostomy. However, there is little information on patient safety improvement methods with this approach. The effect of a checklist on patient safety for bedside ultrasound-guided pleural procedures was evaluated. METHODS: A prospective study of ultrasound-guided pleural procedures from September 2007 to June 2010 was performed. Ultrasound guidance was routine practice for all patients under the institution's care and the freehand method was used. All operators took a half-day training session on basic thoracic ultrasound and were supervised by more experienced operators. A 14-item checklist was introduced in June 2009. It included systematic thoracic scanning and a safety audit. Clinical and safety data are described before (Phase I) and after (Phase II) the introduction of the checklist. RESULTS: There were 121 patients in Phase I (58.7 ± 18.9 years) and 134 patients in Phase II (60.2 ± 19.6 years). Complications occurred for 10 patients (8.3%) in Phase I (six dry taps, three pneumothoraces, one haemothorax) and for 2 patients (1.5%) in Phase II (one significant bleed, one malposition of chest tube) (P = 0.015). There were no procedure-related deaths. The use of the checklist alone was associated with fewer procedure-related complications. This was independent of thoracostomy rate, pleural effusion size and pleural fluid ultrasound appearance. CONCLUSIONS: A pleural checklist with systematic scanning and close supervision may further enhance safety of ultrasound-guided procedures. This may also help promote safety while trainees are learning to perform these procedures.

A review of current bronchoscopic interventions for obstructive airway diseases.

Obstructive diseases of the airway are a diverse group, although they share in common airway narrowing as a sequel to inflammation, which leads to increased work of breathing. Optimal treatment strategies for this heterogeneous group of asthma, chronic bronchitis and emphysema should be multidimensional and embrace pharmacological and nonpharmacological means as well as surgery in a highly select group of patients with emphysema. We review the current status of the bronchoscopic interventions that have been in development for the past decade with the objectives of providing better symptom control in asthma and palliation in individuals with emphysema who are otherwise poor candidates for lung volume reduction surgery.

Mediastinal re-staging of non small-cell lung cancer.

Selected patients with non small-cell lung cancer (NSCLC) with mediastinal lymph node involvement may have a survival benefit from surgical resection, particularly if mediastinal nodal down-staging occurs after induction therapy and complete resection is achieved with lobectomy. Accurate re-staging of the mediastinum after induction therapy is therefore crucial in determining prognosis and subsequent treatment. Non-invasive imaging techniques usually require a confirmatory tissue sampling method to improve the accuracy of mediastinal re-staging. As in the initial staging of the mediastinum, minimally invasive endosonography-guided needle sampling techniques such as endobronchial ultrasound-guided fine-needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration show promise in re-staging the mediastinum, though invasive surgical re-staging remains the gold standard. Despite a lower sensitivity in the mediastinal re-staging of NSCLC, EBUS-TBNA with or without EUS-FNA may still be the preferred initial mediastinal re-staging technique.

Endoscopic mediastinal staging of lung cancer.

The advent of endoscopic ultrasound-guided sampling procedures such as endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has lead to significant advances in the mediastinal diagnosis and staging of lung cancer. These endoscopic techniques can be performed in the outpatient setting under conscious sedation and local anesthesia, in contrast to the surgical standard, mediastinoscopy (MS), which requires operating theatre time and general anesthesia. Proponents of mediastinoscopy have always emphasized the advantages of mediastinoscopy, namely its sensitivity even with a low prevalence of mediastinal metastases and its low false negative rate. Newer endoscopic techniques such as EBUS-TBNA are showing sensitivities exceeding that of mediastinoscopy, even in the setting of an equally low prevalence of mediastinal metastases. However, endoscopic techniques have double the false negative rate of mediastinoscopy. As the tracheobronchial route and esophageal route provide almost complete access to mediastinal lymph nodes, these endoscopic techniques are complementary rather than competing. When used in combination, it is possible mediastinoscopy may be superseded. The challenge however, is how best to select the appropriate endoscopic procedures to accurately stage lung cancer in the most cost-effective manner.

Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking. METHODS: We performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions. RESULTS: There were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA. CONCLUSIONS: Our results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.

First endoscopic procedure for diagnosis and staging of mediastinal lymphadenopathy.

AIM: To compare a first diagnostic procedure of transbronchial needle aspiration (TBNA) with selection of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or TBNA for mediastinal lymphadenopathy. METHODS: Sixty-eight consecutive patients with mediastinal lymphadenopathy on computed tomography (CT), who required cytopathological diagnosis, were recruited. The first 34 underwent a sequential approach in which TBNA was performed first, followed by EUS-FNA if TBNA was unrevealing. The next 34 underwent a selective approach where either TBNA or EUS-FNA was selected as the first procedure based on the CT findings. RESULTS: The diagnostic yield of TBNA as the first diagnostic procedure in the sequential approach was 62%. In the selective approach, the diagnostic yield of the first procedure was 71%. There was no significant difference in the overall diagnostic yield, but there were significantly fewer combined procedures with the selective approach. CONCLUSION: Selecting either EUS-FNA or TBNA as the first diagnostic procedure achieved a comparable diagnostic yield with significantly fewer procedures than performing TBNA first in all patients.

Severe community-acquired Acinetobacter baumannii pneumonia: an emerging highly lethal infectious disease in the Asia-Pacific.

BACKGROUND AND OBJECTIVE: Patients with community-acquired Acinetobacter baumannii (AB) pneumonia have been reported from subtropical countries. We investigated the epidemiology, clinical and microbiological characteristics of community-acquired pneumonia (CAP) due to AB in Singapore. METHOD: A retrospective case series was performed over a 21-month period at two institutions. RESULTS: From 1 January 2007 to 30 September 2008, eight patients were diagnosed with CAP due to AB. Seven had bacteraemia and five were sputum culture-positive. The median age at presentation was 58.5 years (range 45-76 years). Five patients (71.4%) acquired the pneumonia in the warmer months of June to September. Presentation was acute, with a median duration of 2.5 days (range 1-7 days). The median Acute Physiology and Chronic Health Evaluation II score was 28.5 (range 6-36). Six patients presented with septic shock, lactic acidosis, acute kidney injury and respiratory failure, necessitating ICU care; five of these patients eventually died. All patients received empirical antibiotics, including third-generation cephalosporins, which were inactive against the organism. All isolates were susceptible to ampicillin/sulbactam, ciprofloxacin, co-trimoxazole, aminoglycosides and imipenem. CONCLUSIONS: Community-acquired AB pneumonia have a fulminant course. In a region endemic for melioidosis and severe community-acquired Klebsiella pneumoniae, the challenge lies in rapid identification and initiation of appropriate empirical antibiotics to improve the survival of patients with AB CAP.

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).

BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): maximizing the diagnostic procedure and the use of low-volume lung biopsies.

BACKGROUND: Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospital constraints, the practicalities of incorporating mutational analysis in every newly diagnosed case of NSCLC, namely, maximizing tissue acquisition during the diagnostic procedure and determining the maximum quantity and quality of DNA sequence data available from these biopsies. METHODS: Sixty-eight Chinese patients were enrolled. Thirty-five underwent surgical resections for early-stage tumors. Thirty-three underwent diagnostic procedures, i.e., needle aspirates under bronchoscopic or computed tomographic/fluoroscopic guidance, or forceps biopsies via bronchoscopy. Separate samples for research purposes were obtained from these 33 patients during the diagnostic procedure. All samples were analyzed for mutations in EGFR exons 18 to 21, p53 exons 4 to 9, and Kras exon 2. RESULTS: No deaths occurred in this study. Success rates in obtaining sequence data from surgical samples versus low-volume samples for EGFR, p53, and Kras were 100% versus 85%, 100% versus 82%, and 100% versus 85%, respectively. Sequencing nine polymerase chain reaction products from each low-volume sample resulted in the exhaustion of all extracted DNA from three samples. CONCLUSIONS: Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.

EUS-guided FNA immediately after unrevealing transbronchial needle aspiration in the evaluation of mediastinal lymphadenopathy: a prospective study.

BACKGROUND: Transbronchial needle aspiration (TBNA) and EUS-guided FNA (EUS-FNA) are minimally invasive diagnostic approaches to mediastinal lymphadenopathy. Rapid on-site cytopathologic evaluation (ROSE) may facilitate the decision whether to proceed to a second procedure in the same session. The aim of this study was to determine the utility of TBNA with ROSE, combined with the option for immediate EUS-FNA in a single-session approach to mediastinal lymphadenopathy. METHODS: We prospectively recruited 20 patients (12 men; mean age 66.7 +/- 10.2 years) with mediastinal lymphadenopathy on CT who required cytopathologic evaluation. Bronchoscopy was first performed with TBNA and ROSE. If this was unrevealing, EUS-FNA was performed immediately afterward with ROSE. All procedures were performed with the patient under local anesthesia and sedation. RESULTS: TBNA specimens were deemed adequate on-site in 13 patients, and EUS-FNA was performed in the remaining 7 patients. TBNA with ROSE was falsely negative in one patient. The diagnostic yield for TBNA and EUS-FNA alone was 65% and 86%, respectively. This single-session approach provided a yield of 90%, with no complications. The final diagnoses were 12 non-small-cell lung cancer, two small-cell lung cancer, one metastatic adenocarcinoma, two sarcoidosis, one tuberculosis, one lymphoma, and one with no definitive diagnosis. CONCLUSIONS: Combining TBNA with the option for EUS-FNA immediately after unrevealing TBNA gave a yield approaching that of mediastinoscopy and, therefore, may reduce the need for invasive mediastinal sampling. This single-session endoscopic approach was safe, required only local anesthesia and sedation, was convenient, and obviated the need for patients to return for a second procedure.